Andrea Antosova
@saske.sk
Biophysics
Institute of Experimental Physics
RESEARCH INTERESTS
amyloid, fibrillization, fluorescence, atomic force microscopy, nanoparticles
Scopus Publications
Scopus Publications
Zuzana Bednarikova, Martina Kubovcikova, Iryna Antal, Andrea Antosova, Miroslav Gancar, Jozef Kovac, Radka Sobotova, Vladimir Girman, Diana Fedunova, Martina Koneracka,et al.
Elsevier BV
Veronika Džupponová, Nataša Tomášková, Andrea Antošová, Erik Sedlák, and Gabriel Žoldák
MDPI AG
Thermophilic proteins and enzymes are attractive for use in industrial applications due to their resistance against heat and denaturants. Here, we report on a thermophilic protein that is stable at high temperatures (Ttrs, hot 67 °C) but undergoes significant unfolding at room temperature due to cold denaturation. Little is known about the cold denaturation of thermophilic proteins, although it can significantly limit their applications. We investigated the cold denaturation of thermophilic multidomain protein translation initiation factor 2 (IF2) from Thermus thermophilus. IF2 is a GTPase that binds to ribosomal subunits and initiator fMet-tRNAfMet during the initiation of protein biosynthesis. In the presence of 9 M urea, measurements in the far-UV region by circular dichroism were used to capture details about the secondary structure of full-length IF2 protein and its domains during cold and hot denaturation. Cold denaturation can be suppressed by salt, depending on the type, due to the decreased heat capacity. Thermodynamic analysis and mathematical modeling of the denaturation process showed that salts reduce the cooperativity of denaturation of the IF2 domains, which might be associated with the high frustration between domains. This characteristic of high interdomain frustration may be the key to satisfying numerous diverse contacts with ribosomal subunits, translation factors, and tRNA.
Andrea Antosova, Miroslav Gancar, Zuzana Bednarikova, Jozef Marek, Eva Bystrenova, and Zuzana Gazova
Springer Science and Business Media LLC
AbstractThere is limited knowledge regarding α-lactalbumin amyloid aggregation and its mechanism. We examined the formation of α-lactalbumin amyloid fibrils (α-LAF) in the presence of cations (Mg2+, Ca2+, Na+, K+, NH4+, and Cs+) in the form of chloride salts at two concentrations. We have shown that studied cations affect the conformation of α-lactalbumin, the kinetics of its amyloid formation, morphology, and secondary structure of α-LAF in a different manner. The higher salts concentration significantly accelerated the aggregation process. Both salt concentrations stabilized α-lactalbumin's secondary structure. However, the presence of divalent cations resulted in shorter fibrils with less β-sheet content. Moreover, strongly hydrated Mg2+ significantly altered α-lactalbumin's tertiary structure, followed by Na+, NH4+, K+, and weakly hydrated Cs+. On the other hand, Ca2+, despite being also strongly hydrated, stabilized the tertiary structure, supposedly due to its high affinity towards α-lactalbumin. Yet, Ca2+ was not able to inhibit α-lactalbumin amyloid aggregation. Graphic abstract
Diana Fedunova, Andrea Antosova, Jozef Marek, Vladimir Vanik, Erna Demjen, Zuzana Bednarikova, and Zuzana Gazova
MDPI AG
Amyloid fibrils draw attention as potential novel biomaterials due to their high stability, strength, elasticity or resistance against degradation. Therefore, the controlled and fast fibrillization process is of great interest, which raises the demand for effective tools capable of regulating amyloid fibrillization. Ionic liquids (ILs) were identified as effective modulators of amyloid aggregation. The present work is focused on the study of the effect of 1-ethyl-3-methyl imidazolium-based ILs with kosmotropic anion acetate (EMIM-ac) and chaotropic cation tetrafluoroborate (EMIM-BF4) on the kinetics of lysozyme amyloid aggregation and morphology of formed fibrils using fluorescence and CD spectroscopy, differential scanning calorimetry, AFM with statistical image analysis and docking calculations. We have found that both ILs decrease the thermal stability of lysozyme and significantly accelerate amyloid fibrillization in a dose-dependent manner at concentrations of 0.5%, 1% and 5% (v/v) in conditions and time-frames when no fibrils are formed in ILs-free solvent. The effect of EMIM-BF4 is more prominent than EMIM-ac due to the different specific interactions of the anionic part with the protein surface. Although both ILs induced formation of amyloid fibrils with typical needle-like morphology, a higher variability of fibril morphology consisting of a different number of intertwining protofilaments was identified for EMIM-BF4.
A. Antosova, M. Gancar, Z. Bednarikova, J. Marek, D. Zahn, S. Dutz, and Z. Gazova
Elsevier BV
Iryna Khmara, Matus Molcan, Andrea Antosova, Zuzana Bednarikova, Vlasta Zavisova, Martina Kubovcikova, Alena Jurikova, Vladimir Girman, Eva Baranovicova, Martina Koneracka,et al.
Elsevier BV
Marianna Barbalinardo, Andrea Antosova, Marta Gambucci, Zuzana Bednarikova, Cristiano Albonetti, Francesco Valle, Paola Sassi, Loredana Latterini, Zuzana Gazova, and Eva Bystrenova
Springer Science and Business Media LLC
Andrea Antosova, Zuzana Bednarikova, Martina Koneracka, Iryna Antal, Jozef Marek, Martina Kubovcikova, Vlasta Zavisova, Alena Jurikova, and Zuzana Gazova
Wiley
Nanoparticles have great potential to be used in various biomedical applications, including therapy or diagnosis of amyloid-related diseases. The physical and chemical properties of iron oxide superparamagnetic nanoparticles (MNPs) functionalized with different amino acids (AAs), namely, with lysine (Lys), glycine (Gly), or tryptophan (Trp), have been characterized. The cytotoxicity of nanoparticles and their effect on amyloid fibrillization of lysozymes in vitro was also verified. The AA-MNPs under study are nontoxic to human SHSY5Y neuroblastoma cells. Moreover, the AA-MNPs were able to significantly inhibit lysozyme amyloid fibrillization and destroy amyloid fibrils. Kinetic studies revealed that the presence of AA-MNPs affected lysozyme fibrillization, namely, the lag phase and steady-state phase of the growth curves. The most effective activities were observed for Trp-MNPs, which revealed the importance of aromatic rings in the structure of AAs used as coating agents. The obtained results indicate the possible application of these AA-MNPs in the treatment of amyloid diseases associated with lysozyme or other amyloidogenic proteins.
Ruiyan Zhang, Ning Zhang, Marzieh Mohri, Lisha Wu, Thomas Eckert, Vadim B. Krylov, Andrea Antosova, Slavomira Ponikova, Zuzana Bednarikova, Philipp Markart,et al.
American Chemical Society (ACS)
Insulin and lysozyme share the common features of being prone to aggregate and having biomedical importance. Encapsulating lysozyme and insulin in micellar nanoparticles probably would prevent aggregation and facilitate oral drug delivery. Despite the vivid structural knowledge of lysozyme and insulin, the environment-dependent oligomerization (dimer, trimer, and multimer) and associated structural dynamics remain elusive. The knowledge of the intra- and intermolecular interaction profiles has cardinal importance for the design of encapsulation protocols. We have employed various biophysical methods such as NMR spectroscopy, X-ray crystallography, Thioflavin T fluorescence, and atomic force microscopy in conjugation with molecular modeling to improve the understanding of interaction dynamics during homo-oligomerization of lysozyme (human and hen egg) and insulin (porcine, human, and glargine). The results obtained depict the atomistic intra- and intermolecular interaction details of the homo-oligomerization and confirm the propensity to form fibrils. Taken together, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation.
Andrea Antosova, Zuzana Bednarikova, Martina Koneracka, Iryna Antal, Vlasta Zavisova, Martina Kubovcikova, Josephine W. Wu, Steven S.-S. Wang, and Zuzana Gazova
Elsevier BV
Su-Chun How, Yu-Hong Cheng, Chun-Hsien Lo, Jinn-Tsyy Lai, Ta-Hsien Lin, Zuzana Bednarikova, Andrea Antosova, Zuzana Gazova, Josephine W. Wu, and Steven S.-S. Wang
Elsevier BV
Slavomira Ponikova, Jana Kubackova, Zuzana Bednarikova, Jozef Marek, Erna Demjen, Andrea Antosova, Andrey Musatov, and Zuzana Gazova
Elsevier BV
Slavomíra Poniková, Andrea Antošová, Erna Demjén, Dagmar Sedláková, Jozef Marek, Rastislav Varhač, Zuzana Gažová, and Erik Sedlák
Springer Science and Business Media LLC
Quan Van Vuong, Zuzana Bednarikova, Andrea Antosova, Pham Dinh Quoc Huy, Katarina Siposova, Nguyen Anh Tuan, Mai Suan Li, and Zuzana Gazova
Royal Society of Chemistry (RSC)
The structure of glyco-acridines determines their impact on insulin amyloid aggregation and newly introduced geometrical descriptors allow us to distinguish different binding affinities.
Man Hoang Viet, Katarina Siposova, Zuzana Bednarikova, Andrea Antosova, Truc Trang Nguyen, Zuzana Gazova, and Mai Suan Li
American Chemical Society (ACS)
Self-assembly of Aβ peptides into amyloid aggregates has been suggested as the major cause of Alzheimer's disease (AD). Nowadays, there is no medication for AD, but experimental data indicate that reversion of the process of amyloid aggregation reduces the symptoms of disease. In this paper, all 8000 tripeptides were studied for their ability to destroy Aβ fibrils. The docking method and the more sophisticated MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) method were employed to calculate the binding affinity and mode of tripeptides to Aβ fibrils. The ability of these peptides to depolymerize Aβ fibrils was also investigated experimentally using atomic force microscopy and fluorescence spectroscopy (Thioflavin T assay). It was shown that tripeptides prefer to bind to hydrophobic regions of 6Aβ9-40 fibrils. Tripeptides WWW, WWP, WPW and PWW were found to be the most potent binders. In vitro experiments showed that tight-binding tripeptides have significant depolymerizing activities and their DC50 values determined from dose-response curves were in micromolar range. The ability of nonbinding (GAM, AAM) and weak-binding (IVL and VLA) tripeptides to destroy Aβ fibrils was negligible. In vitro data of tripeptide depolymerizing activities support the predictions obtained by molecular docking and all-atom simulation methods. Our results suggest that presence of multiple complexes of heterocycles forming by tryptophan and proline residues in tripeptides is crucial for their tight binding to Aβ fibrils as well as for extensive fibril depolymerization. We recommend PWW for further studies as it has the lowest experimental binding constant.
Peter Kopcansky, Katarina Siposova, Lucia Melnikova, Zuzana Bednarikova, Milan Timko, Zuzana Mitroova, Andrea Antosova, Vasil M. Garamus, Viktor I. Petrenko, Mikhail V. Avdeev,et al.
Elsevier BV
Maria-Magdalena Mocanu, Constanta Ganea, Katarina Siposova, Alexandru Filippi, Erna Demjen, Jozef Marek, Zuzana Bednarikova, Andrea Antosova, Irina Baran, and Zuzana Gazova
Elsevier BV
Quan Van Vuong, Katarina Siposova, Trang Truc Nguyen, Andrea Antosova, Lucia Balogova, Ladislav Drajna, Jan Imrich, Mai Suan Li, and Zuzana Gazova
American Chemical Society (ACS)
While amyloid-related diseases are at the center of intense research efforts, no feasible cure is currently available for these diseases. The experimental and computational techniques were used to study the ability of glyco-acridines to prevent lysozyme amyloid fibrillization in vitro. Fluorescence spectroscopy and atomic force microscopy have shown that glyco-acridines inhibit amyloid aggregation of lysozyme; the inhibition efficiency characterized by the half-maximal inhibition concentration IC50 was affected by the structure and concentration of the derivative. We next investigated relationship between the binding affinity and the inhibitory activity of the compounds. The semiempirical quantum PM6-DH+ method provided a good correlation pointing to the importance of quantum effects on the binding of glyco-acridine derivatives to lysozyme. The contribution of linkers may be explained by the valence bond theory. Our data provide a basis for the development of new small molecule inhibitors effective in therapy of amyloid-related diseases.
Mikhail V. Avdeev, Victor L. Aksenov, Zuzana Gazová, László Almásy, Viktor I. Petrenko, Hubert Gojzewski, Artem V. Feoktystov, Katarina Siposova, Andrea Antosova, Milan Timko,et al.
International Union of Crystallography (IUCr)
The helical structure of amyloid protofilaments of hen egg white lysozyme was analyzed by small-angle neutron scattering (SANS) and atomic force microscopy (AFM). The structure of these formations in bulk solutions was adequately described by SANS in terms of a simplified model of a helix with spherical structural units. The found main helix parameters (pitch and effective diameter) are consistent with the results of AFM analysis for amyloid fibrils adsorbed on a mica surface. Both methods reveal a strong isotope effect on the structure of amyloid fibrils with respect to the substitution of heavy for light water in the solvent. Specific details responsible for the structural differences when comparing SANS and AFM data are discussed from the viewpoint of methodological aspects, the influence of different (native and adsorbed) amyloid states and sample preparation.
Katarina Siposova, Eva Bystrenova, Andrea Antosova, Martina Koneracka, Vlasta Zavisova, Peter Kopcansky, and Zuzana Gazova
AEPress, s.r.o.
Presence of protein amyloid deposits is associated with pathogenesis of amyloid-related diseases. Insulin amyloid aggregates have been reported in a patient with diabetes undergoing treatment by injection of insulin. We have investigated the interference of insulin amyloid aggregation with two Fe3O4-based magnetic fluids. The magnetic fluids are able to inhibit insulin amyloid fibrillization and promote disassembly of amyloid fibrils. The cytotoxic effect of amyloid fibrils is attenuated in presence of magnetic fluids probably due to reduction of the fibrils. We suggest that present findings propose the potential use of Fe3O4-based magnetic fluids as the therapeutic agents targeting insulin-associating amyloidosis.
Andrea Antosova, Zuzana Gazova, Diana Fedunova, Eva Valusova, Eva Bystrenova, Francesco Valle, Zuzana Daxnerova, Fabio Biscarini, and Marian Antalik
Elsevier BV
Katarina Siposova, Martina Kubovcikova, Zuzana Bednarikova, Martina Koneracka, Vlasta Zavisova, Andrea Antosova, Peter Kopcansky, Zuzana Daxnerova, and Zuzana Gazova
IOP Publishing
Pathogenesis of amyloid-related diseases is associated with the presence of protein amyloid deposits. Insulin amyloids have been reported in a patient with diabetes undergoing treatment by injection of insulin and causes problems in the production and storage of this drug and in application of insulin pumps. We have studied the interference of insulin amyloid fibrils with a series of 18 albumin magnetic fluids (MFBSAs) consisting of magnetite nanoparticles modified by different amounts of bovine serum albumin (w/w BSA/Fe3O4 from 0.005 up to 15). We have found that MFBSAs are able to destroy amyloid fibrils in vitro. The extent of fibril depolymerization was affected by nanoparticle physical–chemical properties (hydrodynamic diameter, zeta potential and isoelectric point) determined by the BSA amount present in MFBSAs. The most effective were MFBSAs with lower BSA/Fe3O4 ratios (from 0.005 to 0.1) characteristic of about 90% depolymerizing activity. For the most active magnetic fluids (ratios 0.01 and 0.02) the DC50 values were determined in the range of low concentrations, indicating their ability to interfere with insulin fibrils at stoichiometric concentrations. We assume that the present findings represent a starting point for the application of the active MFBSAs as therapeutic agents targeting insulin amyloidosis.
Z. Gazova, K. Siposova, M. Koneracka, A. Antosova, V. Zavisova, M. Kubovcikova, D. Fedunova, J. Bagelova, N. Tomasovicova, Z. Daxnerova,et al.
Institute of Physics, Polish Academy of Sciences
Z. Gazovaa,∗, K. Siposova, M. Koneracka, A. Antosova, V. Zavisova, M. Kubovcikova, D. Fedunova, J. Bagelova, N. Tomasovicova, Z. Daxnerova and P. Kopcansky Institute of Experimental Physics, Slovak Academy of Sciences, Kosice, Slovakia Department of Biochemistry, Faculty of Science, Safarik University, Kosice, Slovakia Institute of Biology and Ecology, Faculty of Science, Safarik University, Kosice, Slovakia
Andrea Antosova, Beatrice Chelli, Eva Bystrenova, Katarina Siposova, Francesco Valle, Jan Imrich, Maria Vilkova, Pavol Kristian, Fabio Biscarini, and Zuzana Gazova
Elsevier BV
Andrea Antosova, Martina Koneracka, Katarina Siposova, Vlasta Zavisova, Zuzana Daxnerova, Ivo Vavra, Martin Fabian, Peter Kopcansky, Zuzana Gazova, Urs Häfeli,et al.
AIP
At least twenty human proteins can fold abnormally to form pathological deposits that are associated with several amyloid‐related diseases. We have investigated the effect of four magnetic fluids (MFs)—electrostatically stabilized Fe3O4 magnetic nanoparticles (MF1) and sterically stabilized Fe3O4 magnetic nanoparticles by sodium oleate (MF2, MF3 and MF4) with adsorbed BSA (MF2) or dextran (MF4)—on amyloid aggregation of two proteins, human insulin and chicken egg lysozyme. The morphology, particle size and size distribution of the prepared magnetic fluids were characterized. We have found that MFs are able to decrease amyloid aggregation of both studied proteins and the extent of depolymerization depended on the MF properties. The most effective reduction was observed for MF4 as 90% decrease of amyloids was detected for insulin and lysozyme amyloid aggregates. Our findings indicate that MFs have potential to be used for treatment of amyloid diseases.